Synthesis and Biological Activity of 1-Phenylsulfonyl-4-Phenylsulfonylaminopyrrolidine Derivatives as Thromboxane A 2 Receptor Antagonists

Marusawa, Hiroshi; Setoi, Hiroyuki; Sawada, Akikatsu; Kuroda, Akio; Seki, Jiro; Motoyama, Yukio; Tanaka, Hirokazu

doi:10.1016/s0968-0896(01)00397-2

Cited by 15 publications

(10 citation statements)

References 26 publications

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“…The conversion of 2 to (4R)-N-tBoc-cis-4-hydroxy-D-proline methyl ester (4) (81% yield, two steps) was followed by the protection of the alcohol moiety with tert-butyldimethylsilyl (TBDMS) group to give (4R)-N-tBoc-cis-4-(tert-butyldimethylsilyloxy)-D-proline methyl ester (5) in 94% yield. 20,21) The oxidation of 5 using ruthenium oxide and periodate (NaIO 4 ) gave 6 in 88% yield.…”

Section: Resultsmentioning

confidence: 99%

“…18,[19][20][21][22] tert-Butyl 3-(bromomethyl)-1H-indole-1-carboxylate (10) was obtained as a white solid in a total yield of 85% from indole-3-carbaldehyde (7) in accordance with the method described in the literatures. (4R)-N-tBoc-4-tert-Butyldimethylsilyloxy-4-(N-tBoc-3-indolylmethyl)-D-pyroglutamic Acid Methyl Ester (11) LHMDS was added (1.7 mol/L in THF, 29.10 mL, 50.34 mmol) to a stirred solution of compound 6 (15.67 g, 41.95 mmol) in anhydrous THF (60 mL) under an argon atmosphere at −78°C.…”

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confidence: 99%

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Concise Synthesis of (2R,4R)-Monatin

Amino

2016

Chem. Pharm. Bull.

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Monatin, 4-hydroxy-4-(3-indolylmethyl)-glutamic acid, is a naturally occurring sweet amino acid. The (2R,4R)-monatin isomer has been found to be the sweetest among its four stereoisomers. A concise and efficient synthesis of (2R,4R)-monatin was accomplished by the alkylation of (4R)-N-tert-butoxycarbonyl (tBoc)-4-tert-butyldimethylsilyoxy-D-pyroglutamic acid methyl ester with tert-butyl 3-(bromomethyl)-1H-indole-1-carboxylate to give (4R)-N-tBoc-4-tert-butyldimethylsilyloxy-4-(N-tBoc-3-indolylmethyl)-D-pyroglutamic acid methyl ester, i.e., the lactam form of (2R,4R)-monatin with protecting groups. This was followed by the hydrolysis of the lactam ring and deprotection. The 4-hydroxyl D-pyroglutamic acid derivative was demonstrated to be a suitable precursor for the efficient preparation of (2R,4R)-monatin in high optical purity because the alkylation proceeded in regioselective and stereoselective manners at C4 to form appropriate asymmetric tetra-substituted carbon center; the resulting alkylated pyroglutamic acid derivative was then easily converted into the linear form of monatin.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Concise Synthesis of (2R,4R)-Monatin

Amino

2016

Chem. Pharm. Bull.

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“…Scheme presents an outline of the proposed new synthetic route. The nucleophilic displacement of alcohol 5 is well documented for the Mitsunobu-type reaction using DPPA. , Although the displacement of an activated form ( 6 ) such as the mesylate with sodium azide is known, − direct S N 2 substitutions of a sulfonyl-activated hydroxyproline by simple amines are surprisingly absent from the literature. Some of the rare examples include S N 2 substitution with adenine and a protected l -serine as the nucleophiles.…”

Section: Discussionmentioning

confidence: 99%

“…[α] D = −11.7 (T = 24 °C, c = 1, CHCl 3 ) 1 H NMR (400 MHz; CDCl 3 ) δ 8.32 (m, 2H), 6.50 (m, 1H), 4.5−4.3 (m, 1H), 3.95−3.75 (m, 5H), 3.74 (s, 3H), 3.35−3.2 (m, 1H), 3.05−2.9 (m, 1H), 2.6−2.4 (m, 4H), 2.25−2.05 (m, 2H), 1.48, 1.42 (2s, 9H). 13 (2S,4S)-1-tert-Butyl-2-methyl-4-(4-(pyrimidin-2-yl)piperazin-1-yl)pyrrolidine-1,2-dicarboxylate (7). A Boctrans-4-hydroxy-L-proline methyl ester (5) (10.0 g, 0.041 mol) and Et 3 N (11.4 mL, 0.082 mol) solution in 150 mL of acetonitrile was cooled to 5 °C, and 4-nitrobenzenesulfonyl chloride (12.8 g, 0.057 mol, 1.4 equiv) was added portionwise at 5 °C (±5 °C) throughout the addition.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

New Synthetic Route to a Dipeptidyl Peptidase-4 Inhibitor

Lafrance

Caron

2012

Org. Process Res. Dev.

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A new synthetic route to a dipeptidyl peptidase-4 (DPP4) inhibitor was developed and demonstrated on a multigram scale. This approach takes advantage of the cheap and readily available Boc-trans-4-hydroxy-l-proline methyl ester as starting material which was derivatized through an SN2 reaction. Several leaving groups were studied, and the nosylate group showed superiority over other derivatives. Formation of an amide using the most costly starting material, 3,3-difluoropyrrolidine, was performed late in the synthesis to minimize its economical impact on the overall cost of the API.

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“…10% Pd/C (0.4 g) was added followed by MeOH (50 mL). A solution of 1- tert -butyl-2-methyl-(2 S ,4 R )-4-azidopyrrolidine-1,2-dicarboxylate (3.22 g, 11.92 mmol) 22,24 in MeOH (50 mL) was added, and the suspension was cooled to 0 º C. The flask was evacuated and placed under a balloon of H 2 (g). The stirred suspension was warmed to room temperature overnight.…”

Section: Experimental Methodsmentioning

confidence: 99%

Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives

Myers

Palte²,

Raines

2019

J. Org. Chem.

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The identification and understanding of structure–activity relationships is vital for rational catalyst design. A kinetic study of the hydrogen–deuterium exchange reaction of cyclohexanone in aqueous solution, as catalyzed by proline derivatives, has revealed valuable structure–activity relationships. In phosphate-buffered solution, cis-4-fluoroproline is more active than the trans isomer, a distinction that appears to originate from a destabilizing interaction between the fluorine atom and phosphate anion during general acid catalyzed dehydration of the carbinolamine intermediate. Trans-4-ammoniumprolines are exceptionally active catalysts owing to favourable Coulombic interactions involving the ammonium group and the alkoxide moiety formed upon 1,2-addition of the proline derivative to the ketone. These results could be used for the optimisation of proline catalysts, especially in transformations where the formation of the putative iminium ion is rate-limiting.

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Synthesis and Biological Activity of 1-Phenylsulfonyl-4-Phenylsulfonylaminopyrrolidine Derivatives as Thromboxane A 2 Receptor Antagonists

Cited by 15 publications

References 26 publications

Concise Synthesis of (2<i>R</i>,4<i>R</i>)-Monatin

Concise Synthesis of (2<i>R</i>,4<i>R</i>)-Monatin

New Synthetic Route to a Dipeptidyl Peptidase-4 Inhibitor

Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives

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